The primary objective of the Center for Research on Environmental Disease (CRED) is to study the mechanisms by which environmental factors may cause or influence human disease and to develop methods for early detection, prevention, and control of environmentally related diseases. The theme for the CRED is to define molecular pathways that lead from environmental exposures to adverse outcomes and to understand the genetic basis for variability in these responses. In the next funding period, CRED members will continue to focus a major research effort on developing and using animal models of human environmental diseases, especially cancer. In addition, the Center will expand research efforts in the area of disease prevention by focusing a greater effort on energy balance and its influence on environmental disease risk. Finally, these research efforts will again be complemented and aided by studies of genetic risk factors in diverse human populations. These areas of focus are selected because they represent major research themes that cut across more than one Research Core. Because the problems of environmental health are complex, requiring an understanding of the sources of chemical and physical stresses in the environment, their modes of transport and transformation, the routes of human exposure, the mechanisms through which the agents exert their effects, and the possible ways their actions may be influenced by modifiers or co-factors, including genetic background, the successful study of these complex problems requires interdisciplinary approaches. To tackle this vast array of problems, the CRED brings together, in an integrated effort, a multidisciplinary group of established scientists with an extremely broad range of expertise. In addition, the CRED will continue to provide these investigators access to sophisticated biochemical, molecular, and analytical techniques to enhance research efforts that revolve around the Center theme. This Center consists of five Research Cores: i) Mechanisms of Toxicity and Cell Death;ii) Cellular Responses to DNA Damage;iii) Molecular Genetics and Environmental Carcinogenesis;iv) Molecular Epidemiology and Ecogenetics;and vi) Targets and Mechanisms of Disease Prevention. The research efforts of these Research Cores will be enhanced by access to the following six Facility Cores: i) Molecular Biology;ii) Transgenic Animals;iii) Histology and Tissue Processing;iv) Cell and Tissue Analysis;v) Analytical Instrumentation;and vi) Biostatistics and Informatics. In addition, an Administrative Core formalizes collaborative interactions and provides for enrichment activities as well as a Pilot Project Program. Finally, a Community Outreach and Education Program also establishes a mechanism to disseminate important research findings of the Center to the general community, as well as provides community education programs with an emphasis on issues related to environmental health sciences.